ULTIMATE: Ultra-Low Tidal Volume Mechanical Ventilation in ARDS Through ECMO
Study Details
Study Description
Brief Summary
Primary Research Question for the Full ULTIMATE Randomized Clinical Trial (RCT): What is the effect of ultra-protective ventilation facilitated by extracorporeal membrane oxygenation (ECMO) versus best current conventional ventilation (CV) on all-cause hospital mortality among patients with early moderate-severe acute respiratory distress syndrome (ARDS)?
Secondary Research Questions: Among patients with early moderate-severe ARDS, what is the effect of ultra-protective ventilation versus CV on: (1) duration of mechanical ventilation; (2) duration of ICU and hospital stay; (3) organ dysfunction; (4) barotrauma; and (5) mortality at other time-points (ICU discharge, 28-day, 60-day)?
The ULTIMATE Pilot Study: Before embarking on a definitive multinational trial to address the questions listed above, the ULTIMATE Pilot Study has these 3 specific feasibility objectives:
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To assess adherence to our explicit mechanical ventilation protocols, with particular focus on delivered tidal volumes in both groups;
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To estimate the rate of patient recruitment and understand barriers to recruitment; and
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To measure and understand the reasons for crossovers or rescue by ECMO in the control group.
In addition, we will monitor safety issues, recording serious adverse events in both groups.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Best conventional ventilation
|
|
| Experimental: Ultra-protective ventilation with ECMO
|
Device: Venovenous ECMO
Venovenous ECMO
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients adhering to the study protocol [Through study completion, an average of 2 years]
Adherence to our explicit ventilation protocols will be adequate if more than 80% of patients have fewer than 10% of monitored values as major protocol violations
- Proportion of patients crossing over to VV ECMO [Through study completion, an average of 2 years]
The number of protocol withdrawals or off-protocol treatment with VV ECMO will be acceptable if fewer than 10% of patients crossover or receive VV ECMO, when not allowed by the protocol
- Number of patients recruited for the study [Through study completion, an average of 2 years]
Patient accrual will be adequate if we recruit 72 patients from 12 sites over 1 year of enrolment
Secondary Outcome Measures
- Ventilator-free days [Up to 30 days]
Duration of alive and free of invasive mechanical ventilation
- Length of stay [Through study completion, an average of 2 years]
ICU and hospital length of stay in survivors and non-survivors
- Number of patients with non-pulmonary organ dysfunction [Up to 30 days]
Using standard definitions
- Number of patients with barotrauma [Up to 30 days]
New barotrauma
- Mortality [Through study completion, an average of 2 years]
At ICU discharge and 30-days
- Health-related quality of life [At 6 months post-randomization]
Health-related quality of life (EQ-5D) via telephone
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years
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Endotracheal mechanical ventilation for ≤ 5 days
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Early moderate-severe ARDS (Berlin Definition) - all of the following conditions for ≤ 48 hours i. PaO2/FiO2 ≤200 with PEEP > 5 cmH2O ii. bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules iii. respiratory failure not fully explained by cardiac failure or fluid overload iv. within one week of a known insult of new or worsening respiratory symptoms
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ARDS severity criterion - either 1 of:
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PaO2/FiO2 ≤ 150 mm Hg, on PEEP ≥ 10 cm H2O and FiO2 ≥ 0.5
Exclusion Criteria:
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Currently receiving any form of ECMO (e.g., venovenous, venoarterial, or hybrid configuration)
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Chronic hypercapnic respiratory failure defined as PaCO2 > 60 mmHg in the outpatient setting
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Home mechanical ventilation (non-invasive ventilation or via tracheotomy), not CPAP
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Actual body weight exceeding 1 kg per centimeter of height
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Severe hypoxemia with PaO2/FiO2 < 80 mmHg
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Expected mechanical ventilation duration < 48 hours
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Treating team is in the process of moving to a palliative mode of care
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Moribund patient not expected to survive 24 hours despite ongoing life-sustaining therapies
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Confirmed diffuse alveolar hemorrhage from vasculitis
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Contraindications to limited anticoagulation (e.g., active GI bleeding, bleeding diathesis)
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Pregnancy - due to unknown effects of PaCO2 changes on placental blood flow
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New York Presbyterian Hospital | New York | New York | United States | 10032 |
| 2 | OHSU Hospital | Portland | Oregon | United States | 97239 |
| 3 | University of Alberta Hospital | Edmonton | Alberta | Canada | |
| 4 | London Health Sciences Centre | London | Ontario | Canada | |
| 5 | University of Ottawa | Ottawa | Ontario | Canada | |
| 6 | Mount Sinai Hospital | Toronto | Ontario | Canada | M5G 1X5 |
| 7 | University Health Network - Toronto General Hospital | Toronto | Ontario | Canada | M5G 2N2 |
| 8 | Sunnybrook Health Sciences Centre | Toronto | Ontario | Canada | |
| 9 | Unity Health | Toronto | Ontario | Canada | |
| 10 | University Health Network - Toronto Western Hospital | Toronto | Ontario | Canada | |
| 11 | Centre Hospitalier Universitaire de Sherbrooke | Sherbrooke | Quebec | Canada |
Sponsors and Collaborators
- University of Toronto
- University Health Network, Toronto
Investigators
- Principal Investigator: Niall Ferguson, MD, MSc, University Health Network, Toronto
- Principal Investigator: Eddy Fan, MD, PhD, University Health Network, Toronto
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ULTIMATE